The research proposed in this grant examines the role of the brain-gut peptide cholecystokinin (CCK) in the modulation of gastric activity and the control of food intake. The program has behavioral, physiological and anatomical aspects and important health related findings can be expected to derive from each of these aspects. CCK is chosen as a representative feedback peptide released from the intestine by the intraluminal presence of digestive products which play a role in the regulation of the digestive process. In experiments with rhesus monkeys, we are proposing to examine the physiological significance of endogenous CCK in the control of carbohydrate, fat and protein emptying, to identify the local gastric mechanisms by which these actions are mediated, and the candidate receptor populations involved in this control. In experiments with rats we are proposing to evaluate the hypothesis that there are multiple and separable mechanisms of action in the mediation of the satiety effect of CCK. These experiments will examine the relative contribution of candidate pyloric, vagal and brainstem CCK receptor populations to CCK satiety by removing these populations, cutting pathways that transmit information from these receptors or lesioning central sites for termination of these pathways. Electrophysiological recording along these pathways will be carried out to attempt to identify and quantify the inputs from the periphery to the brainstem either from the direct activation of these receptor populations or from the gastric events provoked by their activation. Anatomical experiments are proposed to further evaluate the degree to which separate CCK systems may exist. Together these experiments will increase our knowledge of basic physiology of the gastrointestinal unit, identify the contribution of CCK to this physiology and illuminate the mechanisms by which CCK modulates food intake.